PD-1 and PD-L1 regulate cellular immunity in canine visceral leishmaniasis

Area of Science:

• Immunology
• Veterinary Medicine
• Parasitology

Background:

• Programmed cell death protein 1 (PD-1) acts as a negative costimulator, crucial in regulating immune responses during chronic infectious diseases.
• Canine visceral leishmaniasis (VL), caused by Leishmania infantum, is a significant chronic infectious disease in dogs, often associated with immune dysregulation.

Purpose of the Study:

• To investigate the expression of PD-1 and its ligands in dogs with visceral leishmaniasis.
• To evaluate the impact of blocking PD-1 and its ligands on immune responses in infected dogs.

Main Methods:

• Analysis of PD-1 and ligand expression in spleen and lymph node cells from dogs with VL.
• Assessment of lymphoproliferative responses to soluble antigen in the presence or absence of PD-1 blocking antibodies.
• Quantification of cytokine (IL-4, IL-10) and nitric oxide (NO) production.

Main Results:

• Elevated expression of PD-1 and its ligands was observed in the spleen of dogs infected with L. infantum.
• Blocking PD-1 successfully restored antigen-dependent lymphoproliferative responses in infected dogs.
• PD-1 blockade modulated the production of IL-4, IL-10, and nitric oxide, indicating immune regulation.

Conclusions:

• Leishmania infantum infection modulates PD-1 and its ligand expression in canine visceral leishmaniasis.
• Blocking PD-1 can restore the impaired immune response in canine VL.
• Targeting the PD-1 pathway presents a promising strategy for therapeutic development in canine leishmaniasis.